1. Field of the Invention
The present invention relates to the production of anhydrosugar alcohols, also known as anhydroalditols or, in some cases, anhydrohexitols. More particularly, the present invention relates to a process for the production of anhydrosugar alcohols from sugar alcohol or monoanhydrosugar alcohol starting materials using elevated temperature and pressure.
2. Related Art
The chemical formation of closed-ring organic molecules has posed many issues for structural organic chemists. This has been particularly true with regard to synthetic reactions involving sugars and polyols, the acid dehydration of which leads to internal anhydro compounds (mono- and dianhydro products). Fleche and Huchette, Staerke 38:26-30 (1985) (hereby incorporated by reference in its entirety).
The earliest work in this area was done on 1,4:3,6-dianhydro-D-mannitol by Faucommier in 1884. Only sporadic work followed until the 1940's and 1950's, when intensive work was done on all possible isomers of 1,4:3,6-dianhydrohexitols. Stoss and Hemmer, Adv. Carbohydrate Chem. and Biochem. 93-173 (1991) (hereby incorporated by reference in its entirety). Since then a large body of chemical literature has developed in this area.
The 1,5:3,6-dianhydrohexitols belong to the so-called “biomass-derived substances,” obtainable from natural products. Therefore, these compounds are classified as “regenerable resources.” Furthermore, 1,4:3,6-dianhydrohexitols, such as isosorbide, can be used as starting materials and intermediates in various organic synthetic reaction schemes. For example, isosorbide is useful in the formation of numerous pharmaceutical compounds, in food production, cosmetic production, plastic and polymer production, and in other industrial uses such as in the production of polyurethane, polycarbonate, polyesters, and polyamides. Stoss and Hemmer, 1991. Examples of specific compounds in which isosorbide is used are isosorbide dimethyl ether, which is useful as an industrial solvent, a pharmaceutical additive, and in personal care products, and isosorbide dinitrate, which is useful as a medication to relieve the pain of angina attacks or reduce the number of such attacks by improving blood flow to the heart.
Of the known isohexides, isosorbide is considered to be that of the highest importance. Stoss and Hemmer (1991) describe putative steps leading from D-glucitol (also referred to in the art as sorbitol) to isosorbide. Acidic media are generally used for dehydrating the sugar alcohol substrate. Especially to enhance the yield and to avoid side reactions, certain modifications of the reaction conditions have been employed over the years, with various impacts on yield of isosorbide product. Stoss and Hemmer (1991).
Several processes for the production of anhydrosugar alcohols (including isohexides such as isosorbide) have been reported. For example, PCT application number PCT/US99/00537 (WO 00/14081), discloses collecting methods and a continuous production method with recycling of organic solvent. Most methods involve the use of concentrated acids and organic solvents. Goodwin et al., Carbohydrate Res. 79:133-141 (1980) have disclosed a method involving the use of acidic-cation-exchange resin in place of concentrated, corrosive acids, but with low yield of isosorbide product. An alternative is the supersaturation-based method, as disclosed in U.S. Pat. No. 4,564,692 (Feldmann, et al., Jan. 14, 1986). However, a need continues in the art for a process for production of very pure isosorbide, at reasonable yields. The above-cited references are hereby incorporated by reference in their entireties.